Autologous Bone Marrow Transplantation In Patients Research Articles

Hemostatic Abnormalities Related to Bone Marrow Transplantation

In forty adult patients, submitted to autologous (n 31) or allogeneic (n 9) bone marrow transplantation (BMT) for hematological malignancies, several hemostatic laboratory parameters were evaluated weekly between day -7 and day +21. At baseline (day-7) the prothrombin time (PT) was always normal, the activated partial thromboplastin time (APTT) was prolonged in 5/40, and the plasma fibrinogen was slightly higher than normal. Fifteen autologous BMT patients were studied further. The baseline plasma activities of natural anticoagulants including antithrombin, protein C and protein S activity, as well as plasminogen and α2-antiplasmin were all within the normal range. Plasma prothrombin fragment Fl+2 and thrombin-antithrombin complex levels were higher than normal, suggesting an hypercoagulable state. During the observation period a significant variation was obtained for plasma fibrinogen (increase) and for protein C (decrease). Further studies are required in order to evaluate the true involvement of the he...

Successful treatment of acute myeloid leukemia beyond first remission with autologous bone marrow transplantation using busulfan/cyclophosphamide and unpurged marrow: the British autograft group experience.

The results in 34 adult patients with acute myeloid leukemia (AML) who have undergone autologous bone marrow transplantation (ABMT) using busulfan and cyclophosphamide (Bu/Cy) in 12 United Kingdom (UK) centers have been analyzed. There were 19 females and 15 males; median age was 40 years (range, 21 to 62 years). Nine patients were in first relapse; 25 were in second remission. The median time of first remission for the whole group was 11.5 months (range, 1 to 56 months). All the patients in first relapse and six patients in second remission received first remission marrow. The leukemia-free survival (LFS) for the patients in first relapse was 33%, with a median follow-up of 20 months. The LFS for the patients in second remission was 48% with a median follow-up of 26 months. The length of second remission exceeds the length of first remission in 14 patients. Considerable toxicity with hemorrhagic cystitis (four patients; none fatal), venoocclusive disease (four patients; one fatal), pneumonitis (four patients; one fatal), intracranial hemorrhage (two patients; two fatal) has occurred. There have been four procedure-related deaths (12%). Hematologic recovery was satisfactory for neutrophils (median time to 0.5 x 10(9)/L, 22 days [range, 11 to 101 days]), but very slow for platelets (median time to 50 x 10(9)/L, 62 days [range, 15 to 1,080 days]). This study suggests that the use of Bu/Cy with ABMT for patients beyond first remission in AML compares favorably with chemotherapy, and although the procedure-related mortality is acceptable, it is associated with protracted platelet recovery.

Circulating erythropoietin levels after bone marrow transplantation: inappropriate response to anemia in allogeneic transplants

We studied 24 recipients of autologous bone marrow transplantation (ABMT) or allogeneic BMT (BMT) to determine whether impaired erythropoietin (Epo) response to anemia could delay full erythropoietic recovery. Observed Epo levels were compared with predicted levels based on the relationship between Epo and hematocrit in 125 control subjects. Circulating Epo levels were normal during conditioning and the early posttransplant period. Between days 21 and 180, Epo levels remained normal in ABMT patients but were inappropriately low for the degree of anemia in BMT patients. Median time to full erythropoietic engraftment was longer in BMT than in ABMT recipients. Circulating Epo returned to appropriate levels after day 180, except in patients with active cytomegalovirus infection. We conclude that impaired Epo response to anemia can contribute to delayed erythropoietic recovery after allogenic BMT. Renal toxicity of ciclosporin, interaction between host and donor marrow, and cytomegalovirus infection might play a role. This study could support the use of recombinant human Epo to accelerate erythropoietic engraftment after BMT.

Circulating erythropoietin levels after bone marrow transplantation: inappropriate response to anemia in allogeneic transplants

Abstract We studied 24 recipients of autologous bone marrow transplantation (ABMT) or allogeneic BMT (BMT) to determine whether impaired erythropoietin (Epo) response to anemia could delay full erythropoietic recovery. Observed Epo levels were compared with predicted levels based on the relationship between Epo and hematocrit in 125 control subjects. Circulating Epo levels were normal during conditioning and the early posttransplant period. Between days 21 and 180, Epo levels remained normal in ABMT patients but were inappropriately low for the degree of anemia in BMT patients. Median time to full erythropoietic engraftment was longer in BMT than in ABMT recipients. Circulating Epo returned to appropriate levels after day 180, except in patients with active cytomegalovirus infection. We conclude that impaired Epo response to anemia can contribute to delayed erythropoietic recovery after allogenic BMT. Renal toxicity of ciclosporin, interaction between host and donor marrow, and cytomegalovirus infection might play a role. This study could support the use of recombinant human Epo to accelerate erythropoietic engraftment after BMT.

Nephrotoxicity in bone marrow transplant recipients receiving aminoglycoside plus cyclosporine oraminoglycoside alone

We performed a retrospective analysis of the medical records of allogeneic bone marrow transplantation (BMT) patients receiving cyclosporine plus an aminoglycoside and autologous BMT patients receiving an aminoglycoside without concurrent cyclosporine in the immediate post-transplant period. Acute nephrotoxicity was not seen in any of the patients. Concomitantly used agents such as acyclovir, vancomycin and amphotericin did not worsen renal function. The present study suggests that aminoglycosides, if carefully monitored, can be safely combined with continuous infusion of cyclosporine without excessive nephrotoxicity.

Serum erythropoietin levels in patients receiving intensive chemotherapy and radiotherapy

To investigate the potential role of recombinant human erythropoietin (rhEpo) in patients receiving intensive cytotoxic therapy, we measured the endogenous levels of Epo in 31 patients undergoing bone marrow transplantation (BMT). Seventeen patients underwent allogeneic BMT and 14 underwent autologous BMT. On average, 10 +/- 4 units of red blood cells (RBCs) were transfused per patient. The mean RBC transfusion requirement of the autologous BMT patients was significantly greater than that of the allogeneic recipients (12 +/- 3 v 8 +/- 4, P less than .01), although both groups were maintained at comparable hematocrits. Epo levels were measured by radioimmunoassay (RIA). For each patient, baseline serum Epo levels were determined at time of admission to the hospital. Subsequent samples were collected within 24 hours of completing chemotherapy and/or radiotherapy, and on days 7, 14, and 28, after BMT. Hematocrits (Hcts) were measured daily. All patients had an initial serum creatinine less than or equal to 1.5 mg/dL. Despite considerable differences in absolute Epo levels among individuals, a characteristic pattern was observed. Following admission to the hospital and initiation of cytotoxic therapy, the average Hct decreased and the average Epo level initially increased. The mean serum Epo levels peaked on day 7 post-BMT (284 +/- 190 mU/mL) and fell steadily thereafter. While the average Hcts on day 7 and on day 28 post-BMT were not significantly different (28 +/- 4.6% v 29 +/- 3.3%, respectively), the average serum Epo levels decreased fourfold (P less than .01) during this same period. Moreover, day 28 post-BMT mean Epo levels were inappropriately low (P less than .05) when compared with a reference population with bone marrow failure and normal controls who had not received cytotoxic therapy. We conclude that the endogenous Epo response appears to be blunted during the 3 to 4 weeks immediately post- BMT. Therefore, clinical trials assessing the efficacy of the administration of rhEpo in the treatment of anemias associated with cytotoxic therapy are warranted.

Serum Erythropoietin Levels in Patients Receiving Intensive Chemotherapy and Radiotherapy

To investigate the potential role of recombinant human erythropoietin (rhEpo) in patients receiving intensive cytotoxic therapy, we measured the endogenous levels of Epo in 31 patients undergoing bone marrow transplantation (BMT). Seventeen patients underwent allogeneic BMT and 14 underwent autologous BMT. On average, 10 +/- 4 units of red blood cells (RBCs) were transfused per patient. The mean RBC transfusion requirement of the autologous BMT patients was significantly greater than that of the allogeneic recipients (12 +/- 3 v 8 +/- 4, P less than .01), although both groups were maintained at comparable hematocrits. Epo levels were measured by radioimmunoassay (RIA). For each patient, baseline serum Epo levels were determined at time of admission to the hospital. Subsequent samples were collected within 24 hours of completing chemotherapy and/or radiotherapy, and on days 7, 14, and 28, after BMT. Hematocrits (Hcts) were measured daily. All patients had an initial serum creatinine less than or equal to 1.5 mg/dL. Despite considerable differences in absolute Epo levels among individuals, a characteristic pattern was observed. Following admission to the hospital and initiation of cytotoxic therapy, the average Hct decreased and the average Epo level initially increased. The mean serum Epo levels peaked on day 7 post-BMT (284 +/- 190 mU/mL) and fell steadily thereafter. While the average Hcts on day 7 and on day 28 post-BMT were not significantly different (28 +/- 4.6% v 29 +/- 3.3%, respectively), the average serum Epo levels decreased fourfold (P less than .01) during this same period. Moreover, day 28 post-BMT mean Epo levels were inappropriately low (P less than .05) when compared with a reference population with bone marrow failure and normal controls who had not received cytotoxic therapy. We conclude that the endogenous Epo response appears to be blunted during the 3 to 4 weeks immediately post-BMT. Therefore, clinical trials assessing the efficacy of the administration of rhEpo in the treatment of anemias associated with cytotoxic therapy are warranted.

Recombinant human granulocyte colony-stimulating factor hastens granulocyte recovery after high-dose chemotherapy and autologous bone marrow transplantation in Hodgkin's disease.

To determine whether recombinant human granulocyte colony-stimulating factor (rhG-CSF) can accelerate granulocyte recovery after high-dose combination chemotherapy with autologous bone marrow transplantation (ABMT) in patients with Hodgkin's disease, we performed a nonrandomized phase II study using historical controls as a comparison. Eighteen relapsed/refractory Hodgkin's disease patients who received cyclophosphamide at 1.5 g/m2/day (days -6 to -3), carmustine (BCNU) at 300 mg/m2 (day -6), and etoposide (VP-16) at 125 mg/m2 every 12 hours (days -6 to -4), followed by ABMT (day 0) were treated with rhG-CSF at 60 micrograms/kg/day for a maximum of 28 days beginning on day 1. rhG-CSF dosage was gradually diminished and stopped once an adequate granulocyte count was maintained. rhG-CSF significantly accelerated absolute granulocyte count (AGC) compared with historical controls recovery to the 100/microL level (median, 9 days v 13 days; P = .103 x 10(-4), 500/microL level (median, 13 days v 22 days; P = 0.189 x 10(-2), and 1000/microL level (median, 16 days v 30 days levels; P = .125 x 10(-5). Platelet recovery to 50,000/microL was not significantly altered (P = .370). rhG-CSF was well tolerated, bone pain and myalgia being the only side effects noted. rhG-CSF hastens granulocyte recovery after high-dose chemotherapy with ABMT in patients with relapsed/refractory Hodgkin's disease without significant toxicity.

Hyperalimentation in autologous bone marrow transplantation for solid tumors. Comparison of total parenteralVersus partial parenteral plus enteral nutrition

Recipients of autologous bone marrow transplantation (ABMT) for solid tumors need nutritional support to maintain their body weight (BW). Severe BW-reduction (9.9%) was noticed retrospectively in ten ABMT patients fed orally, despite intensive counseling or occasional tube feeding. A prospective, randomized study of hyperalimentation (25 g nitrogen (N) and 3400 nonprotein kilocalories) with total parenteral nutrition (TPN) or partial parenteral plus enteral nutrition by tube feeding (PPN/EN) was done in 22 patients. Nutritional assessment included balance measurements of N, Na, K, Cl, P, Ca, Mg, Cu, and Zn, and serial measurements of BW, serum albumin, prealbumin, and transferrin. Both regimens were effective in maintaining BW (maximum percent of change, 2.5) and N-balance. Blood products accounted for an additional N-intake of 13% in both groups. The TPN group had a higher dietary N-intake versus PPN/EN, a positive K balance but negative Ca, Mg, Cu, and Zn balances. More mineral supplementation was given in the PPN/EN group where positive K, Mg, and Zn balances were seen. Visceral proteins and IgG, IgA, and IgM levels were decreased on days 7, 14, and 21. Creatinine clearance increased significantly in both groups. Compared with TPN, the PPN/EN group showed a twofold number of patients with a positive blood culture, although this observation did not reach statistical significance and patients had fewer days of diarrhea (31.1% versus 54.3%, P less than 0.01). Hyperalimentation with PPN/EN is an acceptable alternative to TPN in the nutritional support of ABMT recipients.

Herpes Zoster Infection After Autologous Bone Marrow Transplantation

One hundred fifty-three patients who underwent autologous bone marrow transplant (ABMT) were studied retrospectively to determine the frequency, outcome, and risk-factors associated with varicella-zoster infections (VZV). Forty-three patients (28%) developed VZV infection after transplant. The median onset of infection was the fifth month, with 91% of cases occurring within the first year. Thirty-three patients (77%) had localized herpes zoster, and ten patients (23%) had varicella. Cutaneous dissemination developed in 15% of patients and probable visceral dissemination developed in 5%. Overall morbidity was 25% and included scarring, alopecia, postherpetic neuralgia, and neurologic dysfunction. There were no deaths from VZV infection. The majority of patients (79%) were treated with intravenous (IV) acyclovir. The only significant risk factor associated with VZV infection was the underlying disease. VZV infection occurred most frequently in patients with Hodgkin's and non-Hodgkin's lymphoma (46%) as compared with patients with leukemia (23%) or solid tumors (9%) (P less than .002). The frequency of VZV infection in ABMT patients appears to be comparable to that reported for allogeneic BMT patients and other immunocompromised patients.

Herpes zoster infection after autologous bone marrow transplantation

One hundred fifty-three patients who underwent autologous bone marrow transplant (ABMT) were studied retrospectively to determine the frequency, outcome, and risk-factors associated with varicella-zoster infections (VZV). Forty-three patients (28%) developed VZV infection after transplant. The median onset of infection was the fifth month, with 91% of cases occurring within the first year. Thirty-three patients (77%) had localized herpes zoster, and ten patients (23%) had varicella. Cutaneous dissemination developed in 15% of patients and probable visceral dissemination developed in 5%. Overall morbidity was 25% and included scarring, alopecia, postherpetic neuralgia, and neurologic dysfunction. There were no deaths from VZV infection. The majority of patients (79%) were treated with intravenous (IV) acyclovir. The only significant risk factor associated with VZV infection was the underlying disease. VZV infection occurred most frequently in patients with Hodgkin's and non-Hodgkin's lymphoma (46%) as compared with patients with leukemia (23%) or solid tumors (9%) (P less than .002). The frequency of VZV infection in ABMT patients appears to be comparable to that reported for allogeneic BMT patients and other immunocompromised patients.

Lymphocytes after Autologous and Allogenic Bone Marrow Transplantation

Lymphocyte reconstitution after bone marrow transplantation (BMT) was analyzed using two-color flow-cytometry in 18 patients and the differences between allogenic and autologous BMT were studied. The CD8 (+) CD11b (+) and CD8 (+) Leu7 (+) suppressor subsets were increased while the CD4 (+) 2H4 (+) suppressor inducer subset was decreased in both groups after BMT. These variations of suppressor associated subsets persisted for more than 100 days and were considered to be related to immunologic abnormalities in post-BMT patients. In addition, Ia (+) T cells were increased in both autologous and allogenic BMT patients. This increase appears not to be caused by reaction to allo-antigens, but rather reflects the reconstitution of the lymphocyte system after BMT. In contrast, the CD16 (+) NK cell subset was increased specifically in allogenic BMT patients and only for a short time following transplantation.

T-Lymphocyte Subsets in the Lesional Skin of Allogeneic and Autologous Bone Marrow Transplant Patients

Cutaneous biopsy specimens obtained from bone marrow transplant (BMT) patients, most with graft-vs-host disease (GVHD), were analyzed for infiltration by helper, cytotoxic, and suppressor T lymphocytes and natural killer cells. Lesional skin from patients with early mild GVHD and drug reactions showed a CD4/CD8 ratio of 5.0 or more, but later biopsy specimens from patients with acute GVHD and the majority of sections from those with chronic GVHD showed a CD4/CD8 ratio of 0.8 to 3.0 due to increased numbers of presumably cytotoxic cells. Significant numbers of suppressor (CD11 +/- CD16b-) cells were found in only one patient with severe chronic GVHD. Natural killer cells were not found. Preliminary examination of lesional skin from seven autologous BMT patients showed a similar trend of decreased CD4/CD8 ratios in the three patients with a syndrome that resembled GVHD. Analysis of CD4/CD8 ratios in serial biopsy specimens from patients with GVHD may allow more accurate monitoring of the progression of cutaneous GVHD and may help to elucidate the mechanism of development of the GVHD-like reaction in autologous BMT patients.

T-lymphocyte subsets in the lesional skin of allogeneic and autologous bone marrow transplant patients

T-lymphocyte subsets in the lesional skin of allogeneic and autologous bone marrow transplant patients

Cytomegalovirus Infection After Autologous Bone Marrow Transplantation With Comparison to Infection After Allogeneic Bone Marrow Transplantation

AbstractCytomegalovirus (CMV) infection was detected in 65 of 143 (45%) autologous bone marrow transplant (BMT) patients. CMV pneumonitis occurred in only 2% of the patients and CMV retinitis occurred in none. Infection occurred in half of the 40 initially seronegative patients and 47% of the 94 initially seropositive patients. Among initially seropositive patients, platelet recovery was slower in infected patients than in those not infected (97 v 35 days median, P - .003), and neutrophil recovery was slightly delayed in infected patients (31 days v 24 days, P =. 02). Although the incidence of CMV infection was comparable in autologous and allogeneic BMT patients, CMV pneumonitis was less frequent in autologous BMT patients (2% v 12%, P < .001). The risk for CMV pneumonitis in autologous BMT patients was comparable with that in allogeneic BMT patients without graft-v-host disease (GVHD) (2% v 6%), but significantly lower than the risk in allogeneic BMT patients with GVHD (2% v23%, P < .001).

Cytomegalovirus infection after autologous bone marrow transplantation with comparison to infection after allogeneic bone marrow transplantation

Cytomegalovirus (CMV) infection was detected in 65 of 143 (45%) autologous bone marrow transplant (BMT) patients. CMV pneumonitis occurred in only 2% of the patients and CMV retinitis occurred in none. Infection occurred in half of the 40 initially seronegative patients and 47% of the 94 initially seropositive patients. Among initially seropositive patients, platelet recovery was slower in infected patients than in those not infected (97 v 35 days median, P = .003), and neutrophil recovery was slightly delayed in infected patients (31 days v 24 days, P = .02). Although the incidence of CMV infection was comparable in autologous and allogeneic BMT patients, CMV pneumonitis was less frequent in autologous BMT patients (2% v 12%, P less than .001). The risk for CMV pneumonitis in autologous BMT patients was comparable with that in allogeneic BMT patients without graft-v-host disease (GVHD) (2% v 6%), but significantly lower than the risk in allogeneic BMT patients with GVHD (2% v 23%, P less than .001).